all the information, none of the junk | biotech • healthcare • life sciences

Nonprofit Seeds Exonics to Fund Push For CRISPR Duchenne Treatment

Two newly approved drugs slow the progression of the rare and deadly Duchenne muscular dystrophy, but nothing on the market actually reverses the march of the disease. An emerging group of experimental gene therapy and gene editing treatments designed to do so are creeping towards human clinical testing, however, and one of them has just landed in the hands of a new Boston startup, Exonics Therapeutics.

The startup has been seeded with $5 million in funding from CureDuchenne Ventures, a subsidiary of the nonprofit group CureDuchenne. It plans to advance the scientific work of University of Texas Southwestern Medical Center molecular biologist Eric Olson, who has been trying to use the gene editing technology CRISPR-Cas9 to develop a long-lasting treatment for Duchenne.

Patients with Duchenne, who are primarily boys, lose ability to walk by their teens, and often die from complications like respiratory or heart failure at a young age. For years, theses patients had no treatment options. But last September, Sarepta Therapeutics (NASDAQ: SRPT) became the first to win FDA approval of a Duchenne drug, eteplirsen (Exondys 51), and Marathon Pharmaceuticals followed with the second FDA-approved Duchenne-treating drug, deflazacort (Emflaza), earlier this month.

Neither of these treatments are cures, however. Sarepta’s drug is approved for a subset of Duchenne patients, roughly 13 percent with a specific genetic malfunction, for which it is supposed to slow the progression of the disease. Deflazacort is a steroid already widely available in other countries, also meant to help slow Duchenne. Gene therapy and gene editing offer a potentially much longer lasting solution by supplying genetic instructions for a patient’s body to produce a muscle-protecting protein, dystrophin, that people with Duchenne lack.

Olson’s work, which has become the basis for Exonics, uses an adeno-associated virus—a commonly used delivery tool for gene therapy—to deliver CRISPR-Cas9 into the body. CRISPR-Cas9 is essentially a pair of molecular scissors guided to a cell’s nucleus by a strand of RNA, where it snips out a defective gene—in Exonics’s case, a mutation that prevents the production of dystrophin—and replaces it with a functioning one. The approach, if ultimately successful, could lead to a treatment for up to 80 percent of Duchenne patients.

To be clear, however, there is no human clinical evidence that CRISPR can be used safely and effectively in humans. Trials of the technology are just beginning this year in other diseases like cancer and genetic blindness, and it wouldn’t be surprising to see unexpected problems emerge as these therapies progress forward—it’s taken decades, for instance, for gene therapy to get where it is today, and there are just two gene therapies approved in Europe and none in the U.S. Exonics says it expects additional preclinical data next month, but didn’t say how far it is from human clinical testing.

Jak Knowles, the managing director of CureDuchenne Ventures, is Exonics’s president and interim CEO. Cristina Csimma, former president and CEO of rare disease drug accelerator Cydan, is the executive chairman of Exonics. Olsen is the company’s chief science adviser.

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com Follow @benthefidler